The engineering of ontologies that define the entities in an application area and the relationships among them has become essential for modern work in biomedicine. Ontologies help both humans and computers to manage burgeoning numbers of data. The need to annotate, retrieve, and integrate high-throughput data sets, to process natural language, and to build systems for decision support has set many communities of investigators to work building large ontologies. The Protg system has become an indispensable open-source resource for an enormous internationa community of scientists-supporting the development, maintenance, and use of ontologies and electronic knowledge bases by biomedical investigators everywhere. The number of registered Protg users has grown from 3,500 in 2002 to more than 195,000 users as of this writing. To date, however, the use of ontologies in biomedicine has been limited by the complexity of the ontology-development tools, which often make ontologies inaccessible to many biomedical scientists. In this proposal, we will develop new methods and tools that will significantly lower the barrier of entry for ontology development, expanding Protg to provide intuitive and user-friendly ontology-acquisition methods throughout the ontology lifecycle. Our plan entails five specific aims. First, we will develop methods that enable initial specification of ontology terms in an informal manner, using lists and diagrams. Scientists will be able to start modeling their domain without having to think in terms of formal ontological distinctions. Second, we will provide intuitive, easy-to-use tools for ontology specification that will aid developers as they start to formalize their models. Third, we will track the requirements that an ontology must address and develop novel methods for evaluating ontology coverage based on these requirements. Fourth, for ontologies that inherently have complex internal structure that cannot be represented fully using only simple ontology constructs, we will develop methods that will create templates covering regular structures in the ontology. Scientists will then be able to fill out forms based o these templates, with Protg generating the corresponding logical structure in the background. Fifth, we will continue to expand and support the thriving Protg user community, as it expands to include the biomedical scientists who will now be able to build the ontologies to support their data-driven research and discoveries.